A Phase Ⅱ Study of RC108 in Combination With Furmonertinib for the First-line Treatment of EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC

A Randomized, Open, Controlled, Multicenter Phase II Clinical Study of RC108 in Combination With Furmonertinib Versus Furmonertinib for the First-Line Treatment of EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC

Evaluate the efficacy and safety of RC108 in combination with Furmonertinib against Furmonertinib for treatment of EGFR mutation combined with MET-positive unresectable locally advanced or recurrent metastatic NSCLC

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Furmonertinib Mesilate Tablets Monotherapy; Drug: RC108

Detailed Description

Primary objective: Evaluate the efficacy and safety of RC108 in combination with Furmonertinib against Furmonertinib for treatment of EGFR mutation combined with MET-positive unresectable locally advanced or recurrent metastatic NSCLC Secondary objective: Evaluate the pharmacokinetic and immunogenicity characteristics of RC108 in combination with Furmonertinib

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Heping Liu; Phone Number: +86-010-65384976; Email: heping.liu@remegen.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Chest Hospital,Capital Medical Unniversity
  • Beijing, China
    • Recruiting
    • The Fifth Medical Center of Chinese People's Liberation Army General Hospital
  • Binzhou, China
    • Recruiting
    • Binzhou Medical University Hospital
    • Contact: Fangling Ning
  • Changchun, China
    • Recruiting
    • Jilin Cancer Hospital
  • Changsha, China
    • Recruiting
    • The Second Xiangya Hospital of Central South University
    • Contact: fang Ma
  • Changzhou, China
    • Recruiting
    • Changzhou Cancer hospital
    • Contact: Tong Zhou
  • Chengdu, China
    • Recruiting
    • Sichuan Cancer Hospital
    • Contact: yang Wei
  • Chengdu, China
    • Recruiting
    • West China hospitial of SiChuan University
    • Contact: Panwen Tian
  • Chongqing, China
    • Recruiting
    • Chongqing University Cancer Hospitai
  • Fuzhou, China
    • Recruiting
    • Fujian Cancer Hospital
    • Contact: Jing Zhang
  • Ganzhou, China
    • Recruiting
    • Ganzhou cancer Hospitial
    • Contact: Shoujun Guo
  • Guangzhou, China
    • Recruiting
    • Affiliated Cancer Hospital of Guangzhou Medical University
  • Guilin, China
    • Recruiting
    • The Second Affiliated Hospital of Guilin Medical University
  • Guilin, China
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
    • Contact: Bihui Li
  • Hangzhou, China
    • Recruiting
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin, China
    • Recruiting
    • Harbin Medical University Cancer Hospital
    • Contact: yan Yu
  • Hefei, China
    • Recruiting
    • Anhui Provincial Cancer Hospital
    • Contact: Changlu Hu
  • Hefei, China
    • Recruiting
    • The First hospitial of Anhui Medicine University
    • Contact: Yiruo Zhang
  • Jinan, China
    • Recruiting
    • Shandong Cancer Hospital
    • Contact: Xiangjiao Meng
  • Jinan, China
    • Recruiting
    • Jinan Central Hospital
    • Contact: Meili Sun
  • Lanzhou, China
    • Recruiting
    • The First hospitial of Lanzhou University
    • Contact: Xiaoming Hou
  • Linyi, China
    • Recruiting
    • Linyi People's Hospital
    • Contact: Guixiang Weng
  • Shenyang, China
    • Recruiting
    • THE FIRST HOSPITAI OF CHINA MEDICAL UNIVERSITY,No. 155, Nanjing North Street, Heping District, Shenyang City, Liaoning Province
  • Shijiazhuang, China
    • Recruiting
    • The Fourth Hospital of Hebei Medical University
  • Taiyuan, China
    • Recruiting
    • Shanxi Cancer Hospital
  • Taizhou, China
    • Recruiting
    • Taizhou hospitial of Zhejiang province
    • Contact: Dongqing Lv
  • Tianjin, China
    • Recruiting
    • Tianjin Chest Hospital
  • Wuhan, China
    • Recruiting
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Contact: Ruiguang Zhang
  • Xiangyang, China
    • Recruiting
    • Xiangyang Central Hospital
    • Contact: Tienan Yi
  • Yibin, China
    • Recruiting
    • The Second People's Hospital of Yibin City
    • Contact: Jie Chen
  • Yiyang, China
    • Recruiting
    • Yiyang Central Hospital
    • Contact: Bing Zhang
  • Yueyang, China
    • Recruiting
    • Yueyang Central Hospital
    • Contact: Jie Weng
  • Yunnan, China
    • Recruiting
    • Yunnan Cancer Hospital
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily participate in the study and signed the ICF;
2. Male or female, aged 18-75 years;
3. All participants to be enrolled must be diagnosed with histopathologically or cytologically confirmed, unresectable locally advanced (stage IIIB/IIIC )or recurrent metastatic NSCLC (stage IV ) and not amendable to curative surgery or radiation as assessed by investigator;
4. For previously locally advanced or recurrent metastatic disease not treated with systemic antitumor therapy;
5. Carring 1 of 2 common EGFR mutations clearly associated with EGFR-TKI sensitivity (i.e., exon 19 deletion or L858R) and MET positivity;
6. Ability to provide at least 6 sections of tumor tissue specimens for staining and testing；
7. ECOG PS score 0 or 1；
8. At least one measurable lesion according to RECIST v1.1 criteria；
9. Expected survival ≥ 12 weeks;
10. Adequate bone marrow and organ function；
11. Female subjects of childbearing potential or male subjects whose partners are of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose, during which time the female subject is not breastfeeding and the male subject avoids sperm donation.

Exclusion Criteria:

1. Subjects with the presence of meningeal metastases, spinal cord compression, or active brain metastases；
2. Received ADC or MET inhibitors；
3. Suffering from refractory nausea and vomiting, chronic gastrointestinal disorders, inability to swallow pharmaceutical preparations, or previous major bowel resection that may prevent adequate absorption, distribution, metabolism, or excretion of oral medications;
4. Subjects with uncontrolled tumor-related pain；
5. Use of an investigational drug or major surgery within 4 weeks before the first dose;
6. Received any live vaccine within 28 days prior to the first dose or plan to be vaccinated during the study;
7. Subjects with uncontrolled or severe cardiovascular disease;
8. Presence of clinically uncontrollable third interstitial effusion;
9. Presence of severe lung disease, including but not limited to active tuberculosis, interstitial lung disease requiring treatment, radiation pneumonitis, etc.
10. Toxicity due to prior antineoplastic therapy has not recovered to National Cancer Institute Commonly Used Criteria Terminology for Generic Adverse Events, Version 5.0, Grade 0-1;
11. Persistent grade ≥2 sensory or motor neuropathy;
12. Active infections requiring systemic IV antibiotic therapy within 7 days before the first dose, allowing routine antimicrobial prophylaxis;
13. Positive test result for Human Immunodeficiency Virus (HIV) or history of Acquired Immune Deficiency Syndrome (AIDS);
14. Active hepatitis B or HCV-positive subjects;
15. Received systemic corticosteroid therapy with >10 mg/day prednisone or other immunosuppressive medications within 2 weeks before randomization;
16. Other malignant tumor within 5 years before signed the informed consent form;
17. Known hypersensitivity or delayed hypersensitivity to RC108, certain components of Furmonertinib or similar drugs or any contraindication to the drug;
18. Poor compliance and unable to complete the study procedures as assessed by investigator;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 1L, EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC	Drug: Furmonertinib Mesilate Tablets Monotherapy; Furmonertinib; Other Names: Furmonertinib; Drug: RC108; RC108 in Combination With Furmonertinib; Other Names: RC108 For Injection；
Active Comparator: Arm 2; 1L, EGFR-Mutated Combined MET-Positive Unresectable Locally Advanced or Recurrent Metastatic NSCLC	Drug: Furmonertinib Mesilate Tablets Monotherapy; Furmonertinib; Other Names: Furmonertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Investigator-assessed ORR	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	24 months
Progression-free survival (PFS)	Investigator-assessed PFS	24 months
Disease Control Rate (DCR)	Investigator-assessed DCR	24 months
Duration of Response (DoR)	Investigator-assessed DoR	24 months
Overall survival (OS)	Investigator-assessed OS	45 months
Incidence of RC108 anti-drug antibody (ADA)	Incidence, occurrence time and ADA titer of positive RC108 ADA and neutralizing antibodies	24 months
Pharmacokinetic profile of RC108	Peak and trough concentrations of RC108 total antibody (TAb), conjugated antibody (ADC), free MMAE	24 months

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Study Director: Yongchang Zhang, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 30, 2025
• First Submitted That Met QC Criteria: April 30, 2025
• First Posted (Actual): May 8, 2025

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 13, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Aflutinib
• Other Study ID Numbers: RC108-C006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No